Caregivers' perspectives on health-related quality of life in young children with TB and respiratory illnesses.

BACKGROUND: There is a lack of holistic health-related quality of life (HRQoL) measures for young children with respiratory disease, especially in low- and middle-income countries (LMICs). We aimed to understand caregivers' perceptions of the relevance of common HRQoL domains for children with respiratory diseases, including TB. METHODS: This study was nested in a prospective observational cohort of children presenting with respiratory symptoms presumptive of pulmonary TB. We conducted 10 semi-structured interviews to explore caregivers' perceptions of the five commonly measured HRQoL domains: physical health, social support, emotional and psychological wellbeing, and schooling. We used case descriptive analysis and thematic coding. RESULTS: Caregivers considered all five domains to be relevant. The socio-economic context framed their responses, with QoL requiring sufficient basic resources for children. HRQoL experiences varied according to the severity of the child's symptoms, but not between TB and non-TB illnesses. Manifestations in the psychological domain were difficult to distinguish from the emotional domain. Social support included broad support for family members, indirectly benefiting the children. Caregivers were concerned about their children's early developmental milestones and future schooling. CONCLUSION: This exploratory study shows that HRQoL domains are relevant but require adaptation to be applicable for young children affected by respiratory illnesses living in LMICs.

CONTEXTE: Il existe un manque de mesures holistiques de la qualité de vie liée à la santé (HRQoL) pour les jeunes enfants atteints de maladies respiratoires, en particulier dans les pays à revenu faible ou intermédiaire (LMIC). Nous avons cherché à comprendre la perception qu'ont les soignants de la pertinence des domaines communs de la HRQoL pour les enfants atteints de maladies respiratoires, dont la TB. MÉTHODES: Cette étude était imbriquée dans une cohorte observationnelle prospective d'enfants présentant des symptômes respiratoires présomptifs de TB pulmonaire. Nous avons mené 10 entretiens semi-structurés pour explorer les perceptions des soignants sur les cinq domaines de la HRQoL communément mesurés : santé physique, soutien social, bien-être émotionnel et psychologique, et scolarité. Nous avons utilisé une analyse descriptive des cas et un codage thématique. RÉSULTATS: Les soignants considèrent que les cinq domaines sont pertinents. Le contexte socio-économique encadrait leurs réponses, la QoL nécessitant des ressources de base suffisantes pour les enfants. Les expériences de QoL variaient en fonction de la gravité des symptômes de l'enfant, mais pas entre les maladies TB et non TB. Les manifestations dans le domaine psychologique étaient difficiles à distinguer du domaine émotionnel. Le soutien social comprenait un large soutien aux membres de la famille, ce qui profitait indirectement aux enfants. Les soignants étaient préoccupés par les premiers stades de développement de leurs enfants et par leur future scolarité. CONCLUSION: Cette étude exploratoire montre que les domaines de la QoL sont pertinents mais nécessitent une adaptation pour être applicables aux jeunes enfants atteints de maladies respiratoires vivant dans les LMIC.

Long-stay medical-surgical intensive care unit patients in South Africa: Quality of life and mortality 1 year after discharge.

BACKGROUND: Although mortality is the primary measure of critical care outcome, the health-related quality of life (HRQOL) of survivors is often diminished. There is a paucity of South African research on HRQOL in intensive care unit (ICU) survivors. OBJECTIVES: To evaluate the 1-year post-discharge data of long-stay ICU patients, a group known to consume 20 - 40% of ICU resources. METHODS: A 1-year prospective observational study was conducted in a multidisciplinary medical-surgical ICU. Adult patients who were mechanically ventilated beyond 6 days were included. Clinical and mortality data were collected. Pre-admission and 6- and 12-month HRQOL were measured with the Short Form-36 questionnaire. Physical and mental component summary scores (PCS and MCS) were calculated. Associations between 12-month mortality and poor HRQOL scores were determined. RESULTS: Of 119 patients enrolled, 40.3% had sustained trauma, 19.3% were post-surgical and 40.3% had medical conditions; 29.2% were HIV-positive (HIV status was known for 74.8% of the cohort). The hospital and 12-month mortality rates were 42.9% and 57.4% (n=66/115), respectively. Age, longer ICU stay, higher disease severity scores and vasopressor use were associated with 12-month mortality. The survivors' median PCS and MCS at 6 and 12 months were significantly lower compared with pre-admission scores (both p<0.001). At 12 months, 53.1% of survivors demonstrated a poor PCS and 42.9% a poor MCS. Associations with poor 12-month PCS included longer ICU stay, male gender and trauma, while trauma and sepsis were associated with a poor 12-month MCS. Among the 19 trauma survivors, 78.9% had a poor MCS and/or PCS. Of previously employed patients, 54.8% were unemployed at 12 months. CONCLUSIONS: Patients ventilated beyond 6 days in a multidisciplinary ICU had a high mortality. Poor HRQOL at 12 months post discharge was frequently observed among survivors. Trauma was associated with poor 12-month outcomes. These findings highlight the need to further explore the outcomes of long-stay ICU patients in Africa.

Maternal and neonatal outcomes of COVID-19 in a high-risk pregnant cohort with and without HIV.

BACKGROUND: The impact of SARS-CoV-2 infection in pregnant women living with HIV (PLHIV) has not been described previously. OBJECTIVES: To describe the clinical presentation and outcomes of a cohort of women with high-risk pregnancies with confirmed COVID-19 to determine whether risk factors for disease severity and adverse outcomes of COVID-19 differed in pregnant women without HIV compared with PLHIV. METHODS: We prospectively enrolled pregnant women with COVID-19 attending the high-risk obstetric service at Tygerberg Hospital, Cape Town, South Africa, from 1 May to 31 July 2020, with follow-up until 31 October 2020. Women were considered high risk if they required specialist care for maternal, neonatal and/or anaesthetic conditions. Common maternal or obstetric conditions included hypertensive disorders, morbid obesity (body mass index (BMI) ≥40 kg/m2) and diabetes. Information on demographics, clinical features, and maternal and neonatal outcomes was collected and compared for PLHIV v. pregnant women without HIV. RESULTS: One hundred women (72 without HIV and 28 PLHIV) with high-risk pregnancies had laboratory-confirmed COVID-19. Among the 28 PLHIV, the median (interquartile range) CD4 count was 441 (317 - 603) cells/µL, and 19/26 (73%) were virologically suppressed. COVID-19 was diagnosed predominantly in the third trimester (81%). Obesity (BMI ≥30 in n=61/81; 75%) and hypertensive disorders were frequent comorbidities. Of the 100 women, 40% developed severe or critical COVID-19, 15% required intensive care unit admission and 6% needed invasive ventilation. Eight women died, 1 from advanced HIV disease complicated by bacteraemia and urosepsis. The crude maternal mortality rate was substantially higher in women with COVID-19 compared with all other deliveries at our institution during this period (8/91 (9%) v. 7/4 058 (0.2%); p<0.001). Neonatal outcomes were favourable. No significant differences in COVID-19 risk factors, disease severity, and maternal/neonatal outcome were noted for PLHIV v. those without HIV. CONCLUSIONS: In this cohort of high-risk pregnant women, the impact of COVID-19 was severe, significantly increasing maternal mortality risk compared with baseline rates. Virally suppressed HIV infection was not associated with worse COVID-19 outcomes in pregnancy.

Comparing laboratory costs of smear/culture and Xpert® MTB/RIF-based tuberculosis diagnostic algorithms.

SETTING: Cape Town, South Africa, where Xpert® MTB/RIF was introduced as a screening test for all presumptive tuberculosis (TB) cases. OBJECTIVE: To compare laboratory costs of smear/culture- and Xpert-based tuberculosis (TB) diagnostic algorithms in routine operational conditions. METHODS: Economic costing was undertaken from a laboratory perspective, using an ingredients-based costing approach. Cost allocation was based on reviews of standard operating procedures and laboratory records, timing of test procedures, measurement of laboratory areas and manager interviews. We analysed laboratory test data to assess overall costs and cost per pulmonary TB and multidrug-resistant TB (MDR-TB) case diagnosed. Costs were expressed as 2013 Consumer Price Index-adjusted values. RESULTS: Total TB diagnostic costs increased by 43%, from US$440 967 in the smear/culture-based algorithm (April-June 2011) to US$632 262 in the Xpert-based algorithm (April-June 2013). The cost per TB case diagnosed increased by 157%, from US$48.77 (n = 1601) to US$125.32 (n = 1281). The total cost per MDR-TB case diagnosed was similar, at US$190.14 and US$183.86, with 95 and 107 cases diagnosed in the respective algorithms. CONCLUSION: The introduction of the Xpert-based algorithm resulted in substantial cost increases. This was not matched by the expected increase in TB diagnostic efficacy, calling into question the sustainability of this expensive new technology.

Global-to-local policy transfer in the introduction of new molecular tuberculosis diagnostics in South Africa.

SETTING: Lack of innovation in diagnostics has contributed to tuberculosis (TB) remaining a global health challenge. It is critical to understand how new diagnostic technologies are translated into policies and how these are implemented. OBJECTIVE: To examine policy transfer for two rapid molecular diagnostic tests, GenoType(®) MDRTBplus and Xpert(®) MTB/RIF, to understand policy development, uptake and implementation in South Africa. METHODS: A policy transfer analysis framework integrating the key dimensions of policy transfer into one coherent model was used. Two phases of key informant interviews were undertaken with a wide range of stakeholders. RESULTS: Both tests were developed through innovative partnerships and responded to urgent public health needs. GenoType was introduced through a process that was more inclusive than that for Xpert. National policy and planning processes were opaque for both tests. Their implementation, maintenance and expansion suffered from poor communication and coordination, insufficient attention to resource implications, technical challenges and a lack of broader health systems thinking. CONCLUSION: Our analysis identified the risks and benefits of partnerships for technological innovation, the complex intersections between global and national actors and the impact of health systems on policy transfer, and the risks of rescue- and technology-focused thinking in addressing public health challenges.

Paediatric thoracoscopy: state of the art.

Brad Rogers reported the first significant use of thoracoscopy in children in the late 1970s. Over the past two decades there has been an exponential growth and expansion of this technique. Many advanced procedures, including lobectomy, repair of tracheo-esophageal fistula, excision of mediastinal tumours and diaphragmatic hernia repairs, are being done routinely in pediatric surgery centres around the world. This article reviews the state of the art of thoracoscopic surgery in children. The author selected five procedures which in his opinion are most relevant for this discussion. The thoracoscopic technique seems to offer a favourable alternative to open surgery, but more clinical research is necessary to confirm the benefits of minimal access surgery.

A survey on the current status of laparoscopic training in paediatric surgery in South Africa.

OBJECTIVES: To document the current status of laparoscopic training of paediatric surgical registrars in South Africa. METHODS: An anonymous questionnaire was distributed. Participants were asked to document their involvement in a number of index laparoscopic procedures during the preceding year, as well as additional non-operative training they received and their satisfaction with their training thus far. RESULTS: All registrars (N=16) completed the questionnaire. Registrars were from the Universities of KwaZulu-Natal, Cape Town, Stellenbosch, Pretoria and the Witwatersrand, and Walter Sisulu University. The ratio of consultants proficient in paediatric laparoscopy to registrars was between 0.6 and 1. Junior registrars were more likely to assist with, and senior registrars more likely to perform, procedures. Registrar satisfaction varied greatly across institutions, with 44% of registrars satisfied with their training. CONCLUSIONS: The consultant-to-registrar ratio is favourable, and high patient load provides opportunity for laparoscopic education. However, there are a number of obstacles to adequate training. These include the feasibility of after-hours laparoscopic surgery and the availability and use of training aids. The introduction of a structured training programme across all institutions will improve laparoscopic proficiency and satisfaction among paediatric surgical registrars in South Africa.

Laparoscopic treatment of type III para-oesophageal hernia.

Type III congenital para-oesophageal hernia is a rare condition in children and is characterised by the herniation of both a substantial portion of the stomach and the gastro-oesophageal junction into the chest. This report describes the laparoscopic repair of 4 para-oesophageal hernias in children between 2002 and 2010. All hernias were treated successfully using the laparoscopic method. There were no recurrences. The laparoscopic repair of a para-oesophageal hernia is technically challenging, but is feasible and safe in the hands of paediatric surgeons familiar with laparoscopic anti-reflux surgery.

Laparoscopic repair of Morgagni diaphragmatic hernia in children.

Minimal invasive surgery allows for excellent visualisation of the diaphragm, and is increasingly used for the repair of diaphragmatic hernias in children. This report describes laparoscopic repairs between 2001 and 2007 of four Morgagni hernias in children. All defects were treated successfully using the laparoscopic method, with no recurrences. The laparoscopic method is an ideal way to treat this type of diaphragmatic hernia.

NT-proBNP measurements in high-risk diabetic patients--a case series from Mamelodi (Gauteng).

UNLABELLED: The prevalence of raised BNP values is unknown in South African urban black populations at risk for heart failure. This study determined the frequency of raised NT-proBNP and the correlates of NT-proBNP in a high-risk diabetic population. METHODS: A cross-sectional convenience sample of diabetic patients at the Mamelodi Hospital diabetes clinic was examined. Data on clinical, biometric, biochemical and a sixminute walk test were collected. RESULTS: Sixty patients (38 female) were examined. The frequency of elevated NT-proBNP was 22% (95% CI; 12-34%). Univariate analysis found systolic blood pressure (BP) (p = 0.007) and duration of diabetes (p = 0.005) to be predictive of an elevated NT-proBNP.

Facilitating phenomenological interviewing by means of reflexology.

The aim of this article is to show how reflexology could facilitate phenomenological interviewing by probing the life-world of individual participants. It presents a hybrid study of phenomenological interviewing and reflexology as a holistic method of health care. In this sense, it is an interparadigmatic study, since it rests on the interface of Western and Oriental thought. This article reports on seven cases which were included in the qualitative, empirical investigation. During the sessions, reflexological readings served as impetus for inquiry into the experiences of the participants, as congestions on reflex points and along meridians were interpreted in terms of physical organs and functions. These readings were related to corresponding emotions as accepted within the reflexology paradigm. It was, however, up to the participants to inform the researcher of events and/or circumstances that caused the emotions. Thus, nonverbal data communicated information that facilitated verbal exchange concerning the life-world of each individual participant.

A comparison of different orbivirus proteins that could affect virulence and pathogenesis.

The factors that determine the virulence and pathogenesis characteristics of bluetongue virus (BTV), African horse sickness virus (AHSV) and other orbiviruses are not well known. With respect to the viral proteins that are expected to play a role it may be assumed that proteins, such as the outer capsid proteins VP2 and VP5, that are involved in the attachment of virus particles to target cells and influence replication efficiency are particularly important. Equally important are viral proteins such as non-structural protein NS3 that influence the release of virus particles from a target host or vector cell. The authors compare the amino acid sequence variation, structural motifs and some phenotypic characteristics of proteins VP2, VP5 and NS3 of different orbiviruses, such as AHSV, BTV and equine encephalosis virus (EEV). The most variable protein is VP2 and a pair-wise alignment of VP2 sequences of different serotypes of both BTV and AHSV indicated variation of between 48% to 64% and 46% to 52% for most isolates, respectively. Several regions of high variability can be identified. VP5 of BTV is much less variable than VP2 but still more so than the cognate AHSV VP5. In contrast, the NS3 protein of AHSV is much more variable than its BTV or EEV counterpart with maximum levels of NS3 variation up to 36% as compared to 10% for BTV. The AHSV NS3 variation is clustered into three discreet phylogenetic groups. All orbivirus NS3/NS3A proteins share a number of highly conserved structural features that include two hydrophobic domains (HD1 and HD2) that are involved in the interaction with the membrane. Most of the NS3 variation is located in HD1 and the adjacent variable region between HD1 and HD2. In the case of AHSV this region only has 13% identity compared to 64% in the case of BTV. NS3 of AHSV is also a highly toxic protein and mutation analysis has indicated that the toxicity is associated with the two hydrophobic domains. Expression of NS3 deletion mutants in bacterial cells has shown that both HD1 and HD2 are necessary for cytotoxicity and that removal of the adjacent N-terminal domains increases cytotoxicity. Preliminary results with different AHSV strains and the corresponding NS3 equivalent have indicated that the membrane permeabilisation effect of the individual NS3 proteins correlate with the permeabilisation effect of the corresponding viruses. These results would suggest that characterisation of the NS3 protein by itself might predict some phenotypic characteristics and potential membrane destabilisation effect of the corresponding virus.

Variation in the NS3 gene and protein in South African isolates of bluetongue and equine encephalosis viruses.

Bluetongue virus (BTV) and equine encephalosis virus (EEV) are agriculturally important orbiviruses transmitted by biting midges of the genus Culicoides. The smallest viral genome segment, S10, encodes two small nonstructural proteins, NS3 and NS3A, which mediate the release of virus particles from infected cells and may subsequently influence the natural dispersion of these viruses. The NS3 gene and protein sequences of South African isolates of these viruses were determined, analysed and compared with cognate orbivirus genes from around the world. The South African BTV NS3 genes were found to have the highest level of sequence variation for BTV (20 %), while the highest level of protein variation of BTV NS3 (10 %) was found between South African and Asian BTV isolates. The inferred NS3 gene phylogeny of the South African BTV isolates grouped them with BTV isolates from the United States, while the Asian BTV isolates grouped into a separate lineage. The level of variation found in the NS3 gene and protein of EEV was higher than that found for BTV and reached 25 and 17 % on the nucleotide and amino acid levels, respectively. The EEV isolates formed a lineage independent from that of the other orbiviruses. This lineage segregated further into two clusters that corresponded to the northern and southern regions of South Africa. The geographical distribution of these isolates may be related to the distribution of the Culicoides subspecies that transmit them.

Membrane association of African horsesickness virus nonstructural protein NS3 determines its cytotoxicity.

The smallest RNA genome segment of African horsesickness virus (AHSV) encodes the nonstructural protein NS3 (24K). NS3 localizes in areas of plasma membrane disruption and is associated with events of viral release. Conserved features in all AHSV NS3 proteins include the synthesis of a truncated NS3A protein from the same open reading frame as that of NS3, a proline-rich region, a region of strict sequence conservation and two hydrophobic domains. To investigate whether these features are associated with the cytotoxicity of NS3 or altered membrane permeability, a series of mutants were constructed and expressed in the BAC-TO-BAC baculovirus-expression system. Our results indicate that mutations in either of the two hydrophobic domains do not prevent membrane targeting of the mutant proteins but abolish their membrane anchoring. This prevents their localization to the cell surface and obviates their cytotoxic effect. The cytotoxicity of NS3 is therefore dependent on its membrane topography and thus involves both hydrophobic domains. NS3 has many of the characteristics of lytic viral proteins that play a central role in viral pathogenesis through modifying membrane permeability.

Variation of African horsesickness virus nonstructural protein NS3 in southern Africa.

NS3 protein sequences of recent African horsesickness virus (AHSV) field isolates, reference strains and current vaccine strains in southern Africa were determined and compared. The variation of AHSV NS3 was found to be as much as 36.3% across serotypes and 27.6% within serotypes. NS3 proteins of vaccine and field isolates of a specific serotype were found to differ between 2.3% and 9.7%. NS3 of field isolates within a serotype differed up to 11.1%. Our data indicate that AHSV NS3 is the second most variable AHSV protein, the most variable being the major outer capsid protein, VP2. The inferred phylogeny of AHSV NS3 corresponded well with the described NS3 phylogenetic clusters. The only exception was AHSV-8 NS3, which clustered into different groups than previously described. No obvious sequence markers could be correlated with virulence. Our results suggest that NS3 sequence variation data could be used to distinguish between field isolates and live attenuated vaccine strains of the same serotype.

Vitamin A status in relation to electroretinographic and electrooculographic findings in HIV infection.

OBJECTIVES: To investigate the electrooculogram (EOG) and an expanded battery of electroretinograms (ERGs) in HIV-infected subjects without retinopathy at two different levels of immunosuppression. Consideration was given to the possible effects of serum levels of vitamin A. METHODS: Two groups of neurologically normal HIV-positive subjects with CD4+ cell counts of <200 (n=17) or >400 (n=19) were contrasted with 20 HIV-negative controls. Rod ERGs, oscillatory potentials and cone ERGs were obtained using ganzfeld stimulation. A sequence of dark- and light-adapted EOG recordings was analyzed to obtain light/dark ratios. The HIV-positive subjects underwent a comprehensive ophthalmologic examination. RESULTS: Intergroup comparisons failed to reveal any significant intergroup differences. Abnormal ERG findings, those exceeding the 98% confidence limits, occurred in 11% (4/36) of the HIV-positive subjects. One of these subjects was hyporetinemic and another had a subnormal retinol level. No subjects had abnormal EOGs. CONCLUSIONS: HIV infection influenced retinal function in 11% of a group of neurologically normal subjects without clinical signs of retinopathy. The profile of electrophysiological findings suggested predominant functional deficits involving middle or inner retinal layers. Vitamin A deficiency and possible vascular changes could account for the observed ERG abnormalities.

Molecular analysis reveals a high mutation frequency in the first untranslated exon of the PPOX gene and largely excludes variegate porphyria in a subset of clinically affected Afrikaner families.

A subset of probands from 11 South African families with clinical and/or biochemical features of variegate porphyria (VP), but without the known protoporphyrinogen oxidase (PPOX) gene defects identified previously in the South African population, were subjected to mutation analysis. Disease-related mutation(s) could not be identified after screening virtually the entire PPOX gene by heteroduplex single-strand conformation polymorphism analysis (HEX-SSCP), although three new sequence variants were detected in exon 1 of the gene in three normal controls. The presence of these single base changes at nucleotide positions 22 (C/G), 27 (C/A) and 127 (C/A), in addition to the known exon 1 polymorphisms I-26 and I-150, indicates that this untranslated region of the PPOX gene is particularly mutation-prone. Furthermore, microsatellite markers flanking the PPOX and alpha-1 antitrypsin (PI) gene, on chromosomes 1 and 14, respectively, were used to assess the probability of involvement of these loci in disease presentation. Common alleles transmitted from affected parent to affected child were determined where possible in the mutation-negative index cases. Allelic frequencies of these <> alleles were compared to findings in the normal population, but no predominant disease-associated allele could be identified. Co-segregation of a specific haplotype with the disease phenotype could also not be demonstrated in a large Afrikaner family. It is concluded that further studies are warranted to determine the genetic factor(s) underlying the autosomal dominant pattern of inheritance in molecularly uncharacterized cases showing clinical symptoms of an acute porphyria.

Cardiac tamponade following umbilical vein catheterisation in a neonate.

Umbilical vein catheterisation (UVC) should not routinely be used in the neonatal intensive care unit, and when it is used special precautions should be taken and guidelines followed. We present an unusual complication which occurred following use of an umbilical vein catheter in a term neonate. This case highlights another potentially lethal complication of UVC, and emphasises the risks associated with the procedure. In order for the benefits of UVC to outweigh the risks, certain guidelines are reviewed. The importance of confirming the position of the catheter tip with both anteroposterior and lateral radiographs is emphasised.